ABSTRACT: National trends and predictors of critical limb ischemia hospitalizations Principal Investigator (Kunihiro Matsushita, MD, PhD). Critical limb ischemia (CLI) is characterized by ischemic non-healing wounds, tissue loss, or rest pain and represents the most severe form of lower extremity peripheral artery disease (PAD). Only a fraction of PAD patients develop CLI, but CLI is a devastating clinical condition. Within one year after the diagnosis, more than half of CLI patients die or undergo leg amputation. Despite rigorous prevalence estimates for PAD based on low ankle-brachial index (ABI), population- based estimates of CLI are limited. A report of national statistics of cardiovascular disease from the American Heart Association solely refers to data from a study simply relying on CLI-related ICD (International Classification of Diseases) codes without validation. These national estimates are critical for policy making and public awareness, and thus more valid estimates are warranted for CLI. Another important gap in our knowledge of the epidemiology of CLI is a lack of long-term prospective cohorts; consequently we know little about specific risk factors for CLI. Since CLI is the first manifestation of PAD for 30-50% of CLI cases, identification of CLI-specific predictors would help identify high risk individuals before they develop CLI, with a potential of targeted prevention approaches. We aim to fill these two gaps (i.e., the lack of data regarding valid national estimates and specific risk factors for CLI) by using two existing data resources: the Atherosclerosis Risk in Communities (ARIC) Study and the National (Nationwide) Inpatient Samples (NIS). Specifically, we will first adjudicate CLI hospitalizations in the ARIC Study based on physicians' chart review. Then, we will develop validation model(s) based on ICD codes and covariates providing the expected probability of ?true? CLI hospitalizations and apply the model(s) to NIS data for estimating trends in CLI hospitalizations from 1998 through 2011. Finally, we will identify major and minor risk factors for CLI in the ARIC Study, with a particular interest in microvascular risk factors. -Aim 1: To estimate trends in CLI hospitalizations in the US -Aim 2: To identify major and minor risk factors for incident CLI hospitalization, distinguishing microvascular vs. macrovascular risk factors in the development of CLI The hybrid of the ARIC Study and NIS will, for the first time, provide accurate estimates for trends in CLI hospitalizations in the US, with implications for healthcare strategies, resource allocation, and public awareness. Also, this project will establish the first long-term community-based cohort with adjudicated CLI cases as an outcome, which will allow us to identify major long-term risk factors for CLI, with implications for early-stage intervention of risk factors to prevent CLI and targeted foot monitoring and care.